Genetic basis of complex traits in schizophrenia

双胞胎和家庭研究表明，精神分裂症有遗传基础。迄今为止，寻找和描述潜在基因的尝试尚未取得成功。造成这种情况的一个主要原因是人们对这种疾病潜在遗传结构的复杂性关注不足。从基因到精神分裂症症状的途径可能涉及神经元和神经回路水平的基本过程，这些过程在个体之间存在差异，这种差异反映在对精神分裂症的分级易感性上。在过去三年中，我们招募了大量至少有一名家庭成员被诊断患有精神分裂症的家庭。先证者和所有参与的一级亲属都接受了神经认知测试，包括持续注意力、工作记忆、信息处理速度、听觉语言学习和执行功能。对该样本的神经认知数据的分析产生了强有力的证据，表明与不相关的正常对照相比，精神分裂症患者及其部分无症状一级亲属的多项指标发生了改变。在这项研究中，我们将系统地搜索人类基因组中与这些措施相关的DNA标记。这将为系统地搜索和描述潜在基因奠定基础。这将使我们更好地了解患精神分裂症的倾向。在个别情况下，这种脆弱性很可能是由一些相对常见的等位基因的高风险组合造成的，这些等位基因有助于基本的神经过程。

Twin and family studies show schizophrenia has a genetic basis. Attempts to find and characterise the underlying genes have not been successful so far. A main reason for this is that insufficient attention has been paid to the complexity of the underlying genetic architecture of the disorder. The pathway from genes to symptoms of schizophrenia is likely to involve elementary processes at neuronal and neural circuitry levels that vary between individuals and this variation is reflected in a graded susceptibility to schizophrenia. During the last three years we have recruited a large number of families with at least one family member diagnosed with schizophrenia. The proband and all participating first-degree relatives have been assessed with a neurocognitive test battery including measures of sustained attention, working memory, speed of information processing, auditory verbal learning and executive function. Analysis of the neurocognitive data on this sample produced strong evidence that several measures are altered in patients with schizophrenia and a proportion of their asymptomatic first-degree relatives compared to unrelated normal controls. In the study we will systematically search the human genome for DNA markers linked to these measures. This will set the stage for the systematic search and characterisation of the underlying genes. This will allow us to better understand the predisposition to develop schizophrenia. In the individual case it is likely that this vulnerability results from a high-risk combination of a number of relatively common alleles which contribute to basic neural processes.